Part 3: Polatuzumab Vedotin Plus Bendamustine and Rituximab Shows Promise in Patients With DLBCL

Bijal Shah, MD, MS

Associate Member

Department of Malignant Hematology

Moffitt Cancer Center

Tampa, FL

During a live virtual event with other physicians, Bijal Shah, MD, MS, reviewed the efficacy and data for the combination of polatuzumab vedotin (Polivy) plus bendamustine (Treanda) and rituximab (Rituxan; pola-BR) for patients with diffuse large B-cell lymphoma (DLBCL). Shah discussed what made this combination effective, but also which adverse events to look out for.

Which data show the most promising efficacy results for pola-BR?

Recently, data have come from a phase 2 trial that evaluated pola-BR [for treatment of R/R DLBCL and R/R follicular lymphoma]. The trial enrolled patients with 1 or more prior lines of therapy, which reflects how R/R is defined in the National Comprehensive Cancer Network guidelines.¹ Patients were required to have an ECOG score of 0 to 2 and no significant peripheral neuropathy, [which can be exacerbated by] polatuzumab. Patients also had to be transplant ineligible.^2,3

Transplant ineligibility is a common requirement for patients in R/R DLBCL trials, but in practice I often find this difficult to define. Patients with a prior allogeneic transplant, a recent autologous transplant, or a history of transformation from indolent disease [also were excluded from] this study. Patients were randomly allocated to receive pola-BR or BR only; randomization was conducted within strata of R/R DLBCL and R/R follicular lymphoma.

The distribution of patients by disease type was good [n = 40 in each disease group]. Some patients had up to 7 prior lines [of therapy], but approximately half of patients had 2 [or fewer] prior lines. About 25% of patients had a prior transplant, and 37.5% of patients had GCB disease.

What was the response to pola-BR in this setting?

Response rates to pola-BR were like what we saw with lenalidomide/tafasitamab: the ORR in the pola-BR arm was 45%, with the majority being CRs [40%].³ Among patients who received BR alone, the ORR was 20%, including a CR rate of 17.5%.

PFS, based on the [analysis done by the] independent review committee, was 9.5 months in the pola-BR arm [compared with 3.7 months in the] BR-only arm. OS was 12.4 months in the pola-BR group compared with 4.7 months in the BR group. What [was not evaluated in this trial] is the effect of polatuzumab plus rituximab.

If we know that bendamustine is not adding much—at least BR did not show much [of an effect in this trial]—then it is unclear whether we need to include bendamustine as a component of this regimen. We often ask ourselves this question for our patients at Moffitt [Cancer Center].

What adverse events (AEs) were associated with pola-BR?

Adverse events [AEs] associated with pola-BR included, not surprisingly, cytopenias. [Grade 3 or 4] thrombocytopenia occurred in 41% of patients, and neutropenia in approximately 46% of patients. What may [be surprising] is that in the BR-only arm, 33% of patients developed grade 3 or 4 neutropenia and [23% of patients developed grade 3 or 4] thrombocytopenia.

Polatuzumab is certainly driving some of the thrombocytopenia. Lymphopenia [did not occur in the] BR arm, and the absence of lymphopenia is something I see in almost all the patients I’ve treated with BR, [including those with] mantle cell lymphoma and DLBCL.

Febrile neutropenia was not very common in either arm of the cohort. High-grade nausea, strangely, was not seen in the pola-BR or the BR arms, which contrasts with what was seen in the BRIGHT study [NCT00877006].⁴ In the pola-BR study, fatigue, decreased appetite, and peripheral neuropathy were common, [occurring in 35.9%, 25.6%, and 43.6% of patients, respectively]. Interestingly, high-grade neuropathy was not seen.³

_REFRENCES

_{1. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 4.2021. Accessed June 6, 2021. https://bit.ly/3geoS5N}

_{2. Sehn LH, Kamdar M, Herrera AF. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Oncol. 2018;36(suppl 15):7507. doi:10.1200/JCO.2018.36.15_suppl.7507}

_{3. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large b-cell lymphoma. J Clin Oncol. 2020;38(2):155-165. doi:10.1200/JCO.19.00172}

_{4. Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014;123(19):2944-2952. doi:10.1182/blood-2013-11-531327}